hPD-1

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C57BL/6Smoc-Pdcd1em1(hPDCD1) /Smoc

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NM-HU-00015

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Official Symbol
Pdcd1

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The endogenous mouse Pdcd1 gene was replaced by human PDCD1(PD-1) gene .
신청분야:Immunotherapy,cancer research,drug screening

검증 데이터

  • Data from flow cytometry (FACS) analysis

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Fig1 . Expression of PD-1 in the activated spleen lymphocytes of humanized PD-1 Homozygous mice is detected by FACS.

  • In vivo validation in a MC38 tumor-bearing model of humanized PD-1 mice

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Fig2 . In vivo anti-tumor effect of an anti-human PD-1 antibody in a humanized mouse model of PD-1. Anti-human-PD-1 drugs significantly inhibited the growth of MC38 tumors in PD-1 mice, demonstrating that the humanized PD-1 mice can be used to assess the anti-human PD-1 antibody. 

A. Mean volume ± SEM of tumor tissues (completed in cooperation with Genscript). 

In vivo validation of anti-tumor efficacy in a MC38 tumor-bearing model of humanized PD-1 mice. Homozygous humanized PD-1 mice were inoculated with MC38 colon cancer cells. After the tumors grew to 100 mm3, the animals were randomly assigned into a control group and a treatment group (n=8). The drug was given twice a week for a total of 4 administrations. The results showed that Keytruda, a drug targeting human PD-1, exerted a very significant anti-tumor effect (p<0.001), demonstrating that the humanized PD-1 mice are a good in vivo model for validating the efficacy of antibodies targeting human PD-1. 

B. Mean volume ± SEM of tumor tissues. C. Mean body weight ± SEM of mice (data were obtained in cooperation with PharmaLegacy).

In vivo dose validation of anti-tumor efficacy in a MC38 tumor-bearing model of humanized PD-1 mice. Homozygous humanized PD-1 mice were inoculated with MC38 colon cancer cells. After the tumors grew to about 90 mm3, the animals were randomly assigned into a control group and a treatment group (n=9). The results showed that the antibodies targeting human PD-1 showed a very significant antitumor effect (p<0.001), and such antitumor effect is dose-dependent.


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Fig3 . In vivo dose validation in a MC38 tumor-bearing model of humanized PD-1 mice. Homozygous humanized PD-1 mice were inoculated with MC38 colon cancer cells. After the tumors grew to 100 mm3, the animals were randomly assigned into a control group and a treatment group (n=8). The drug was given twice a week for a total of 4 administrations.

Case Study

As one of the first five anti-PD-1 drugs with BLAs accepted by CFDA, Sintilimab has shown potent T cell stimulating activity and significant anti-tumor efficacy. (read more)


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Fig4 .  In vivo hPD-1 knock-in mouse model to test anti-tumor efficacy of Sintilimab. (A) Tumor growth inhibition (TGI) of MC38 tumors in hPD-1 knock-in mice of individual animals treated with different doses of Sintilimab. (B) Effect of Sintilimab on percentage changes in mouse body weight(mean). (C) Changes in ratios of tumor infiltrating CD4+, CD8+ and Treg cells. For d8: IgG (n = 2); Sintilimab (n = 2). For d14, n = 3 for all groups. P values were calculated using a two-tailed t-test method.




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Shanghai Model Organisms Center Inc has licensed CRISPR-Cas9 technology from Broad Institute

On Dec 16, 2018, Broad Institute and Shanghai Model Organisms Center Inc (SMOC) has entered into a non-exclusive license agreement under which Broad has granted SMOC worldwide rights to commercialize a service platform for genetically modified mouse models under Broad's intellectual property.

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Milestones

Our vision is to provide researchers all over the world with comprehensive, convenient and professional animal model services to facilitate a simplified and highly-efficient approach towards uncovering the mysteries of life.

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